Abstract The common marmoset ( Callithrix jacchus ) is an important non-human primate model in neuroscience and biomedical research. However, existing 3D resources for this species have mainly focused on brain atlases or keypoint-based pose estimation, and reusable data resources that jointly describe the body surface, fur, articulated structure, and experimental environment remain limited. Here, we present a multimodal dataset designed to reconstruct body– environment interactions of common marmosets in three dimensions. The dataset includes a whole-body surface mesh derived from computed tomography (CT) images, fur representations based on photographic references, a rigged 3D model for pose-driven animation, synchronized behavioral videos from three individuals recorded for approximately 90 hours from eight view-points, 2D and 3D keypoint estimation data, 3D models of the experimental environment constructed from blueprint information, and rendered pseudo-egocentric views generated by integrating pose estimation results with the 3D body and environment models. Technical validation assessed the geometric agreement between the CT-derived mesh and the surface model, the accuracy of 2D and 3D keypoint estimation, the dimensional accuracy of the environment model, and the structural similarity between real and rendered images. This dataset provides a foundation for treating marmoset natural behavior not only as point trajectories but also as a three-dimensional phenomenon involving body shape and its spatial relationship with the environment, thereby enabling applications in behavioral analysis, visualization, synthetic-data generation, and future digital-twin studies.
Summary Episodic memory requires distinguishing similar events occurring at the same location but at different times. While the hippocampus integrates “where” and “when,” the specific roles of the primate dentate gyrus (DG) and CA3 remain elusive. We recorded single-unit activity from freely moving marmosets navigating a spatial maze in a visually impoverished environment. Both hippocampal subfields robustly encoded self-position via neurons selective for stationary epochs at platforms and movement along trajectories, whereas gaze-related coding was minimal. While DG signaled stationary and dynamic self-positions independently, CA3 integrated these elements into conjunctive representations. Critically, only CA3 neurons exhibited strong temporal-order modulation. These findings reveal a feedforward disambiguation process in which CA3 transforms discrete spatial inputs from DG into the integrated spatiotemporal maps essential for episodic memory.
Introduction:Aged non-human primates have been reported to develop tau pathology; however, most studies lack evidence of any associated neurological symptoms. To determine whether spontaneous tauopathy in cynomolgus macaques manifests with neurological symptoms, we evaluated a symptomatic aged monkey (Monkey T) alongside an asymptomatic control (Monkey A). Methods:Two male cynomolgus macaques, aged 33-34 years old at the time of necropsy, were examined. They were evaluated using comprehensive behavioral, pathological, and genetic analyses. Results:Monkey T exhibited progressive neurological symptoms for approximately two years prior to euthanasia, including tremors, nuchal dystonia, and a flexed posture, whereas Monkey A showed no abnormalities. Monkey T demonstrated persistent tremors (6.9 ± 0.7 Hz) and reduced daily motor activity, with modest improvement following L-DOPA administration. Neuropathological evaluation revealed brainstem atrophy and mild depigmentation of the substantia nigra and locus coeruleus. Extensive phosphorylated tau accumulation was observed throughout the brainstem tegmentum, including neurofibrillary tangles, threads, coiled bodies, and astrocytic inclusions. All tau lesions were positive for 4-repeat tau and negative for 3-repeat tau. MAPT sequencing identified four non-pathogenic 3'UTR variants differing between the two monkeys. Isoform analysis showed balanced 3R/4R tau expression in Monkey A but an approximately 1.3-fold increase in 4R tau in Monkey T. Discussion:The parkinsonian symptoms observed in Monkey T were more likely attributable to widespread tau pathology in the brainstem rather than overt degeneration of the nigrostriatal dopaminergic system. This case represents a rare instance of spontaneous tauopathy in an aged cynomolgus macaque, a condition that is extremely difficult to reproduce experimentally. These findings highlight the potential value of cynomolgus macaques as a relevant model for studying sporadic tauopathies, including tau seeding mechanisms.
The identification of neuronal circuits and their specific functions in behavior and disease is essential for understanding the mammalian brain. A promising technique to advance this goal involves the use of lentiviral vectors for specific gene transfer into specific brain circuit. The vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors can introduce genes in neurons at the injection sites. Retrograde lentiviral vectors, such as highly efficient retrograde gene transfer (HiRet) and neuron-specific retrograde gene transfer (NeuRet) vectors, enable the delivery of genetic materials into neurons based on their axonal projections. These lentiviral vectors represent a powerful genetic tool for neuroscience research. Here, we describe a step-by-step experimental procedure for injecting viral vectors into target brain areas using the basal ganglia circuit as example in mice to map their functional properties. This methodology, which integrates local and retrograde gene transfer with optogenetic manipulation, offers a robust framework for investigating the functional organization of neuronal circuits. In demonstrating this approach, this chapter aims to guide researchers to apply these techniques to study brain functions and disorders of interest.
Left-right asymmetry of the brain is well recognized in various animals including C. elegans, drosophila and zebrafish. In primates, most of the brain studies describe side of the brain. However, in spite of huge amounts of accumulating rodent studies on neuroscience, most of rodent studies do not distinguish the brain side. The pig brain is considered to occupy an intermediate position between primates and rodents in terms of structural complexity and brain function. Moreover, the numbers of studies using genetic manipulation of pigs are drastically increasing. So, we investigated microminipig (MMP) brain mesoscopic anatomy focusing on left-right differences of its morphology. Here, we show anterior cingulate cortex, perirhinal cortex, and cerebellum of MMP, are structurally asymmetrical. Anterior cingulate gurus exhibited protrusion and invagination toward the midline on the right and left side, respectively. The left perirhinal cortex has extra gyrus which are not observed on the right side. The cerebellar vermis, paravermis is tilted from the midline and the consequently the cerebellar cortex exhibits asymmetrical morphology. These data demonstrate that MMPs are one of the suitable model animals for investigating cerebral and cerebellar asymmetry. ### Competing Interest Statement The authors have declared no competing interest. Subsidy for national university reform and research infrastructure enhancement from the MEXT, Japan.
The cortico-basal ganglia circuitry plays important roles in the control of various higher-order functions, such as motor control, cognition, and emotion. The thalamostriatal system is involved in learning and switching of behaviors and recovery from cognitive and motor deficits in rodents. Here, we applied selective neural pathway targeting to investigate roles of two representative thalamostriatal pathways arising from the parafascicular nucleus (Pf) and centre médian nucleus (CM) in common marmosets. Targeting of the Pf projecting to the caudate (Cd) resulted in impaired reversal of learned responses in a visual discrimination task, showing increased perseverative errors during the reversal phase. Targeting the CM innervating the putamen (Pu) disturbed acquisition of the visual discrimination. In contrast, elimination of the Pf-Cd or CM-Pu pathway did not alter performance of motor skill learning. Our results indicate that these two thalamostriatal pathways have distinct roles in learning processes of sensory cue-dependent decision-making in nonhuman primates.
The external segment of the globus pallidus (GPe) has long been considered a homogeneous structure that receives inputs from the striatum and sends processed information to the subthalamic nucleus, composing a relay nucleus of the indirect pathway that contributes to movement suppression. Recent methodological revolution in rodents led to the identification of two distinct cell types in the GPe with different fiber connections. The GPe may be regarded as a dynamic, complex and influential center within the basal ganglia circuitry, rather than a simple relay nucleus. On the other hand, many studies have so far been performed in monkeys to clarify the functions of the basal ganglia in the healthy and diseased states, but have not paid much attention to such classification and functional differences of GPe neurons. In this minireview, we consider the knowledge on the rodent GPe and discuss its impact on the understanding of the basal ganglia circuitry in monkeys.
Mutations in Dystonin (DST), which encodes cytoskeletal linker proteins, cause hereditary sensory and autonomic neuropathy 6 (HSAN-VI) in humans and the dystonia musculorum (dt) phenotype in mice; however, the neuronal circuit underlying the HSAN-VI and dt phenotype is unresolved. dt mice exhibit dystonic movements accompanied by the simultaneous contraction of agonist and antagonist muscles and postnatal lethality. Here, we identified the sensory-motor circuit as a major causative neural circuit using a gene trap system that enables neural circuit-selective inactivation and restoration of Dst by Cre-mediated recombination. Sensory neuron-selective Dst deletion led to motor impairment, degeneration of proprioceptive sensory neurons, and disruption of the sensory-motor circuit. Restoration of Dst expression in sensory neurons using Cre driver mice or a single postnatal injection of Cre-expressing adeno-associated virus ameliorated sensory degeneration and improved abnormal movements. These findings demonstrate that the sensory-motor circuit is involved in the movement disorders in dt mice and that the sensory circuit is a therapeutic target for HSAN-VI.
Cardiac angiosarcoma is a malignant tumor derived from vascular endothelium with a dismal prognosis. The imaging findings of cardiac angiosarcoma are nonspecific and endomyocardial and pericardial biopsies have insufficient accuracy. For these reasons, the diagnosis is sometimes difficult. Primary and metastatic tumors tend to bleed easily, causing hemoptysis and neurological symptoms. Brain metastases are not often known to be fatal when they cause hemorrhage. We report a 27-year-old man diagnosed with right atrium angiosarcoma, with metastases in the lung, brain, and bone. The patient had only respiratory symptoms at the first visit and did not show any symptoms derived from brain metastases yet died after 27 days due to hemorrhage from brain metastases. If brain metastasis from angiosarcoma is suspected based on imaging findings, urgent radiotherapy should be considered before histological examination for a definitive diagnosis.
The thalamostriatal projections arising from the intralaminar thalamic nuclei (ILN) constitute the principal source of input information to specified subregions of the striatum, a key structure of the cortico-basal ganglia circuitry. However, the roles of primate ILN in cortico-basal ganglia circuit functions remain unclear. Here, we performed immunotoxin-induced selective targeting of two representative structures of the ILN, the parafascicular nucleus (Pf) and centre médian nucleus (CM) projecting to the caudate nucleus (Cd) and putamen (Pu), respectively, in common marmosets. Elimination of Pf-Cd neurons resulted in impaired reversal learning of a two-choice visual discrimination task, whereas removal of CM-Pu neurons disturbed the task acquisition. No marked impact of such manipulations was observed on either motor skill learning or spontaneous locomotor activity. Our findings reveal that the two thalamostriatal systems play distinct roles in the learning processes of external cue-dependent decision-making in nonhuman primates. ### Competing Interest Statement The authors have declared no competing interest.
The subthalamic nucleus (STN) receives cortical inputs via the hyperdirect and indirect pathways, projects to the output nuclei of the basal ganglia, and plays a critical role in the control of voluntary movements and movement disorders. STN neurons change their activity during execution of movements, while recent studies emphasize STN activity specific to cancelation of movements. To address the relationship between execution and cancelation functions, we examined STN activity in two Japanese monkeys (Macaca fuscata, both sexes) who performed a goal-directed reaching task with a delay that included Go, Cancel, and NoGo trials. We first examined responses to the stimulation of the forelimb regions in the primary motor cortex and/or supplementary motor area. STN neurons with motor cortical inputs were found in the dorsal somatomotor region of the STN. All these STN neurons showed activity changes in Go trials, suggesting their involvement in execution of movements. Part of them exhibited activity changes in Cancel trials and sustained activity during delay periods, suggesting their involvement in cancelation of planed movements and preparation of movements, respectively. The STN neurons rarely showed activity changes in NoGo trials. Go- and Cancel-related activity was selective to the direction of movements, and the selectivity was higher in Cancel trials than in Go trials. Changes in Go- and Cancel-related activity occurred early enough to initiate and cancel movements, respectively. These results suggest that the dorsal somatomotor region of the STN, which receives motor cortical inputs, is involved in preparation and execution of movements and cancelation of planned movements.
Malfunction of the basal ganglia leads to movement disorders such as Parkinson's disease, dystonia, Huntington's disease, dyskinesia, and hemiballism, but their underlying pathophysiology is still subject to debate. To understand their pathophysiology in a unified manner, we propose the "dynamic activity model", on the basis of alterations of cortically induced responses in individual nuclei of the basal ganglia. In the normal state, electric stimulation in the motor cortex, mimicking cortical activity during initiation of voluntary movements, evokes a triphasic response consisting of early excitation, inhibition, and late excitation in the output stations of the basal ganglia of monkeys, rodents, and humans. Among three components, cortically induced inhibition, which is mediated by the direct pathway, releases an appropriate movement at an appropriate time by disinhibiting thalamic and cortical activity, whereas early and late excitation, which is mediated by the hyperdirect and indirect pathways, resets on-going cortical activity and stops movements, respectively. Cortically induced triphasic response patterns are systematically altered in various movement disorder models and could well explain the pathophysiology of their motor symptoms. In monkey and mouse models of Parkinson's disease, cortically induced inhibition is reduced and prevents the release of movements, resulting in akinesia/bradykinesia. On the other hand, in a mouse model of dystonia, cortically induced inhibition is enhanced and releases unintended movements, inducing involuntary muscle contractions. Moreover, after blocking the subthalamic nucleus activity in a monkey model of Parkinson's disease, cortically induced inhibition is recovered and enables voluntary movements, explaining the underlying mechanism of stereotactic surgery to ameliorate parkinsonian motor signs. The "dynamic activity model" gives us a more comprehensive view of the pathophysiology underlying motor symptoms of movement disorders and clues for their novel therapies.
As science and technology evolve, there is an increasing need for promotion of international scientific exchange. Collaborations, while offering substantial opportunities for scientists and benefit to society, also present challenges for those working with animal models, such as non-human primates (NHPs). Diversity in regulation of animal research is sometimes mistaken for the absence of common international welfare standards. Here, the ethical and regulatory protocols for 13 countries that have guidelines in place for biomedical research involving NHPs were assessed with a focus on neuroscience. Review of the variability and similarity in trans-national NHP welfare regulations extended to countries in Asia, Europe and North America. A tabulated resource was established to advance solution-oriented discussions and scientific collaborations across borders. Our aim is to better inform the public and other stakeholders. Through cooperative efforts to identify and analyze information with reference to evidence-based discussion, the proposed key ingredients may help to shape and support a more informed, open framework. This framework and resource can be expanded further for biomedical research in other countries.
Neurons comprising nigrostriatal system play important roles in action selection. However, it remains unclear how this system integrates recent outcome information with current action (movement) and outcome (reward or no reward) information to achieve appropriate subsequent action. We examined how neuronal activity of substantia nigra pars compacta (SNc) and dorsal striatum reflects the level of reward expectation from recent outcomes in rats performing a reward-based choice task. Movement-related activity of direct and indirect pathway striatal projection neurons (dSPNs and iSPNs, respectively) were enhanced by reward expectation, similarly to the SNc dopaminergic neurons, in both medial and lateral nigrostriatal projections. Given the classical basal ganglia model wherein dopamine stimulates dSPNs and suppresses iSPNs through distinct dopamine receptors, dopamine might not be the primary driver of iSPN activity increasing following higher reward expectation. In contrast, outcome-related activity was affected by reward expectation in line with the classical model and reinforcement learning theory, suggesting purposive effects of reward expectation.
Schematic illustration of cortically induced dynamic activity changes of the output nuclei of the basal ganglia (the internal segment of the globus pallidus, GPi and the substantia nigra pars reticulata, SNr) in the healthy and diseased states. The height of the dam along the time course controls the expression of voluntary movements. Its alterations could cause a variety of movement disorders, such as Parkinson's disease and hyperkinetic disorders. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
This study investigated the influence of iterative reconstruction (IR) methods on computed tomography (CT) images when training convolutional neural network (CNN) models to diagnose pulmonary emphysema. To evaluate the influence of the IR algorithm on CNN, the present study comprised two steps: the comparison of noise reduction by IR algorithms using phantom examinations and the change in performance of CNN with IR algorithms using patient data. We retrospectively analyzed 97 patients. Raw CT data were reconstructed using the filtered back-projection (FBP) and adaptive statistical iterative reconstruction V (ASIR-V) algorithms with blending levels of 30